The present invention relates to X-ray imaging of very small formations within human as well as inanimate subjects and is aimed at improving the spatial resolution and the detective quantum efficiency (DQE) of X-ray detectors.
Currently, the highest resolution of digital X-ray imaging systems is up to 25 microns. At this spatial resolution, many pathologies (e.g., micro calcifications in breast cancer) are too small to be visualized at an early stage. In mammography, the resolution of present digital machines is of the order of 50 to 100 μm.
Coronary heart disease is the leading cause of death in the United States today. The field of cardiology is changing its focus towards detection of vulnerable plaque i.e. plaque that is prone to rupture. A large number of patients (especially diabetics) suffer from endothelial dysfunction that occurs at the micro-vascular level. Histological studies show that endothelial dysfunction leads to vulnerable plaque formation that has a high lipid component and a thin fibrous cap of the order of 60 μm. Currently, the composition of a coronary plaque cannot be determined non-invasively and differentiation between vulnerable and stable plaque is not possible due to limited spatial resolution. The early detection of endothelial dysfunction (e.g., via direct visualization of the architecture of the coronary plaque) by imaging at the 1 μm level would allow early treatment of these individuals thus potentially reducing morbidity and mortality in this high-risk cohort.
The presence of calcified coronary artery plaque is the most frequent reason for false positive evaluations, often leading to unnecessary additional testing hence limiting the clinical utility of cardiac CT. It has been shown that dense calcium, due to the limited spatial resolution, creates a “spill-over” effect into adjacent, lower-intensity voxels. The resulting “calcium blooming” obscures the coronary artery lumen and leads to an over-estimation of luminal stenosis. Improving resolution from 0.75 mm in 16 slice scanners to 0.6 mm (600 microns) has partially alleviated this problem. Further improvement to the 1 micron level or lower would be a giant leap for this technology.
A recent paper in the Proceedings of the National Academy of Sciences demonstrated the presence of micro-calcifications (˜10 μm) in the thin fibrous cap of coronary artery plaque. This paper also showed that these micro-calcifications, when present in an area of high circumferential stress (>300 kPa), can magnify the stress to nearly twice this value when the fibrous cap is <65 μm thus leading to plaque rupture. Development of a high resolution digital X-ray detector array can improve detection of such calcification and lead to non-invasive identification of vulnerable plaque.
In demanding applications such as space and aviation, non-destructive testing of engine parts and materials suffer from the same lack of higher spatial resolution and DQE. For example, 3-D X-ray analysis of microscopic flaws in welds is of obvious importance to space technology, and the Jet Propulsion Laboratory at the National Aeronautics and Space Administration is interested in non-destructive evaluation using X-ray imaging.
In Computer-Assisted Tomography (CT), the highest resolution of current technology is 60-80 μm for Xtreme CT and micro CT. As such “small animal imaging”, which currently means mice, is not of great use when imaging even smaller organisms such as fleas and fire-flies.
The above list captures just some of the advantages that would result from this improvement in X-ray resolution. One micron or lower resolution would permit the entire field of radiology to move closer to histo-radiology. This will have an immense impact on the ability of radiologists to diagnose disease with maximum sensitivity and specificity. Such a capability would do for medical imaging what the transistor did for electronics. Success of this project would, indeed, be a “game changer”.
Limitations in spatial resolution are accompanied by a similar lack of the Detective Quantum Efficiency (DQE). DQE is defined as the ability of the imaging system in transforming the absorbed quanta into the final image without introducing additional noise.